Understanding the range of dysfunctions in Parkinson's disease (PD), and the degrees to which they are reversible by pharmacological or electrophysiological treatments, can both increase our understanding of PD therapies and help illuminate critical functions of basal ganglia-cortical circuits in the control of movement. Our previous findings have led us to hypothesize that a major difficulty for patients with Parkinson disease (PD) is in assembling and using new sensorimotor mappings or coordinations. These processes play a major role both in ongoing motor performance and in the acquisition of new skills, and, preliminary data indicate, are not normalized with dopamine (DA) replacement therapy. The present proposal presents seven experiments that are designed to confirm and extend this hypothesis and to investigate the degrees to which deep brain stimulation to the subthalamic nucleus (STN DBS) and DA replacement therapy are able to remediate deficits in sensorimotor control, coordination, and learning. To contrast the effects of these therapies in the same patients, PD patients will be tested ON versus OFF DA replacement prior to their having surgically implanted electrodes, and again after surgery ON and OFF deep brain stimulation (and off medications). The first 4 experiments examine the integration of visual and proprioceptive information, which may be particularly deficient in PD. Subjects will reach to 3D targets presented either visually or kinesthetically with a robot arm under various conditions of visual feedback. The next experiment introduces the requirement that subjects learn to move within a virtual environment as a prerequisite to establishing the new sensorimotor coordinations necessary for accurate target acquisition. Subjects are required to master distortions that create discrepancies between the apparent (virtual) and real (proprioceptively signaled) location of their arms. By dissociating movements from their normal sensory correspondences, subjects'abilities to reconfigure their sensorimotor coordinations will be challenged. The final 2 experiments challenge subjects by requiring them to integrate different motor acts into a complex motor sequence and to be able to compensate for a mechanical perturbation during such an action. By examining a full range of behaviors, and requiring coordinated motor acts, utilization of variable sensory information to guide behavior, and the learning new sensorimotor correspondences, a more systematic assessment of motor control in PD and its benefit by treatment can be obtained. The proposed approach of using such contemporary technologies as 3D immersive virtual realities and robot-guided 3D reaching in examining the degree to which medical versus surgical therapies can ameliorate dysfunctions in PD is unique. PUBLIC HEALTH RELEVANCE: A major question in the treatment of Parkinson's disease is the degree to which different therapies can ameliorate the range of dysfunctions that are a product of the disorder. Surgical implantation of deep brain stimulators, especially those targeted to the subthalamic nucleus, is an increasingly important modality for treatment and restoring function and quality of life in Parkinson's disease. The proposed studies will compare which deficits in sensorimotor control and learning deep brain stimulation therapy versus dopaminergic replacement therapy can reverse and which they cannot, and thus should fill an important gap in the literature that can inform treatment decisions.